Leukemia, MyeloidERVALNCT04406207
Endogenous Retroviruses in Acute Myeloid Leukemia
An observational study of Leukemia, Myeloid, run by Hospices Civils de Lyon.
Trial summary
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for numerous malignant hematologic diseases. Despite recent advances in the field, relapse rates are still high and the first cause of death. The identification of new relevant therapeutic targets is therefore urgently needed. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Leukemia, Myeloid
- What is being tested?
- Demonstration of T cell responses
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2020to 6 Jan 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adults >= 18 years old with acute myeloid leukemia
Who may be able to join
- Acute myeloid leukemia (all subtypes)
- Stem cell transplantation indication
- Non opposition to the study
Who cannot join
- Intensive care unit at diagnosis
About this study
Official title: Human Endogenous Retroviruses in Acute Myeloid Leukemia: Expression and Immune Impact
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for numerous malignant hematologic diseases. Despite recent advances in the field, relapse rates are still high and the first cause of death. The identification of new relevant therapeutic targets is therefore urgently needed.
Human endogenous retroviruses (HERVs) are accounting for 8% of the human genome. While silenced at the steady state (mainly by methylation mechanisms), HERVs reactivations have been described in different conditions such as auto-immune diseases or cancer, leading to an innate and adaptive immune response. Several questions are raised in the field of hematology where few data are available, and the exact role of HERVs in these diseases is still to define.
Read more
Our team is currently working on the role of HERVs in different types of cancer. We developed a bioinformatics approach to identify overexpressed HERVs from RNAseq data. We also developed in vitro assays to assess the immunogenicity of different peptides from HERVs open reading frames and showed that several epitopes shared among different HERVs can induce a specific CD8+ T cell response. More recently, we have analyzed 151 acute myeloid leukemia (AML) RNAseq data from TCGA and identified multiple overexpressed HERVs in this disease. Immunogenicity test are currently ongoing with patient's blood at diagnosis.
The main objective of this part of our project is to analyze the establishment of a HERVs-specific CD8+ T cell response participating in graft-versus-leukemia effect after HSCT for AML patients. Secondary objectives are to analyze relations between this response and different clinical factors such as the onset of GVHD or relapse.
Peripheral blood mononuclear cells (PBMCs) from AML patients will be extracted and frozen at different time point: diagnosis, complete remission (pre-HSCT) and after HSCT (M3, M6 and M12). This prospective protocol is currently ongoing at the Centre Hospitalier Lyon Sud, with around 30 samples already available.
After having selected relevant HERVs, specific dextramers identified by DNA barcode will be synthesized. These dextramers allowing the identification of specific T cell responses directed against up to 1000 epitopes, we will be able to screen specific T cells directed against HERVs overexpressed in AML for most common HLA. Dextramer staining will be performed on PBMCs after thawing. Positive cells will be sorted by flow cytometry and DNA will be expanded by PCR before performing sequencing, allowing the identification of specific sequences by its unique DNA barcode.
The analyze of HERVs-specific CD8+ T cell responses after HSCT will allow us to better define HERVs role in the onset of graft-versus-leukemia effect. A specific T cell response without GvHD will define the relevance of such peptides as tumor specific antigens.
- Conditions
- Leukemia, Myeloid
- Being tested
- Demonstration of T cell responses
- Medical subject headings
- Leukemia, Myeloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Demonstration of T cell responsesOther
Evaluation of HERVs-specific CD8+ T cells before and after hematopoietic stem cell transplantation. Comparison will be made in patients relapsing vs non relapsing patients.
The measurement of these responses will be done by dextramer, allowing precise and specific measurement of the lymphocytes directed against the HERVs of interest.
| Study group | Role | What they receive |
|---|---|---|
| Patients | Patients relapsing or not after hematopoietic stem cell transplantation. Receives: Other: Demonstration of T cell responses |
What is being measured
The primary outcome is the main question the study is designed to answer.
HERVs-specific CD8+ T cells responses
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
Measured: Day 0
HERVs-specific CD8+ T cells responses
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
Measured: At remission <- Day 0 + 1 month
HERVs-specific CD8+ T cells responses
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
Measured: Before transplant <- Day 0 + 3 month
HERVs-specific CD8+ T cells responses
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
Measured: 1 month
HERVs-specific CD8+ T cells responses
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
Measured: 3 months
HERVs-specific CD8+ T cells responses
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
Measured: 6 months
HERVs-specific CD8+ T cells responses
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
Measured: 12 months
HERVs-specific CD8+ T cells responses
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
Measured: At relapse: up to 6 month after day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2020
- Study start1 Jun 2020
- Primary completion6 Jan 2022
- Study completion6 Jan 2022
Why it stopped: COVID-19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, MyeloidStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincent ALCAZER, MD, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04406207
- Sponsor's protocol ID
- 69HCL19_0851
- Acronym
- ERVAL
- Status last verified
- Aug 2022
- First submitted
- 13 May 2020
- Last updated
- 22 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Endogenous Retroviruses in Acute Myeloid Leukemia: Expression and Immune Impact
- ClinicalTrials.gov ID
- NCT04406207
- Acronym / sponsor ID
- ERVAL / 69HCL19_0851
- Conditions
- Leukemia, Myeloid
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: COVID-19
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 6 Jan 2022 (actual)
- Study completion
- 6 Jan 2022 (actual)
- First posted
- 28 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for numerous malignant hematologic diseases. Despite recent advances in the field, relapse rates are still high and the first cause of death. The identification of new relevant therapeutic targets is therefore urgently needed.
Human endogenous retroviruses (HERVs) are accounting for 8% of the human genome. While silenced at the steady state (mainly by methylation mechanisms), HERVs reactivations have been described in different conditions such as auto-immune diseases or cancer, leading to an innate and adaptive immune response. Several questions are raised in the field of hematology where few data are available, and the exact role of HERVs in these diseases is still to define.
Our team is currently working on the role of HERVs in different types of cancer. We developed a bioinformatics approach to identify overexpressed HERVs from RNAseq data. We also developed in vitro assays to assess the immunogenicity of different peptides from HERVs open reading frames and showed that several epitopes shared among different HERVs can induce a specific CD8+ T cell response. More recently, we have analyzed 151 acute myeloid leukemia (AML) RNAseq data from TCGA and identified multiple overexpressed HERVs in this disease. Immunogenicity test are currently ongoing with patient's blood at diagnosis.
The main objective of this part of our project is to analyze the establishment of a HERVs-specific CD8+ T cell response participating in graft-versus-leukemia effect after HSCT for AML patients. Secondary objectives are to analyze relations between this response and different clinical factors such as the onset of GVHD or relapse.
Peripheral blood mononuclear cells (PBMCs) from AML patients will be extracted and frozen at different time point: diagnosis, complete remission (pre-HSCT) and after HSCT (M3, M6 and M12). This prospective protocol is currently ongoing at the Centre Hospitalier Lyon Sud, with around 30 samples already available.
After having selected relevant HERVs, specific dextramers identified by DNA barcode will be synthesized. These dextramers allowing the identification of specific T cell responses directed against up to 1000 epitopes, we will be able to screen specific T cells directed against HERVs overexpressed in AML for most common HLA. Dextramer staining will be performed on PBMCs after thawing. Positive cells will be sorted by flow cytometry and DNA will be expanded by PCR before performing sequencing, allowing the identification of specific sequences by its unique DNA barcode.
The analyze of HERVs-specific CD8+ T cell responses after HSCT will allow us to better define HERVs role in the onset of graft-versus-leukemia effect. A specific T cell response without GvHD will define the relevance of such peptides as tumor specific antigens.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients | – | Other: Demonstration of T cell responsesPatients relapsing or not after hematopoietic stem cell transplantation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adults >= 18 years old with acute myeloid leukemia
Key inclusion criteria (3 listed)
- Acute myeloid leukemia (all subtypes)
- Stem cell transplantation indication
- Non opposition to the study
Key exclusion criteria (1 listed)
- Intensive care unit at diagnosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Demonstration of T cell responsesEvaluation of HERVs-specific CD8+ T cells before and after hematopoietic stem cell transplantation. Comparison will be made in patients relapsing vs non relapsing patients. The measurement of these responses will be done by dextramer, allowing precise and specific measurement of the lymphocytes directed against the HERVs of interest. | Other | Patients |
Primary outcome
HERVs-specific CD8+ T cells responses
Time frame: Day 0
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
HERVs-specific CD8+ T cells responses
Time frame: At remission <- Day 0 + 1 month
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
HERVs-specific CD8+ T cells responses
Time frame: Before transplant <- Day 0 + 3 month
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
HERVs-specific CD8+ T cells responses
Time frame: 1 month
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
HERVs-specific CD8+ T cells responses
Time frame: 3 months
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
HERVs-specific CD8+ T cells responses
Time frame: 6 months
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
HERVs-specific CD8+ T cells responses
Time frame: 12 months
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
HERVs-specific CD8+ T cells responses
Time frame: At relapse: up to 6 month after day 0
HERVs-specific CD8+ T cells responses will be monitored using DNA-barcode dextramers.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vincent ALCAZER, MD principal investigator
Hospices Civils de Lyon
Questions about this trial
What is this clinical trial studying?
An observational study of Leukemia, Myeloid, run by Hospices Civils de Lyon.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HERVs-specific CD8+ T cells responses (time frame: Day 0). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2022.